ATB-346 is a hydrogen sulfide-releasing non-steroidal anti-inflammatory drug (H₂S-NSAID) derived from naproxen, which in preclinical studies has been shown to have markedly reduced gastrointestinal adverse effects. However, its anti-inflammatory properties in humans compared to naproxen are yet to be confirmed. To test this, we used a dermal model of acute inflammation in healthy, human volunteers, triggered by ultraviolet-killed Escherichia coli. This robust model allows quantification of the cardinal signs of inflammation along with cellular and humoral factors accumulating within the inflamed skin. ATB-346 was non-inferior to naproxen in terms of its inhibition of cyclooxygenase activity as well as pain and tenderness. ATB-346 significantly inhibited neutrophil infiltration at the site of inflammation at 4 h, compared to untreated controls. Subjects treated with ATB-346 also experienced significantly reduced pain and tenderness compared to healthy controls. Furthermore, both classical and intermediate monocyte subsets infiltrating the site of inflammation at 48 h expressed significantly lower levels of CD14 compared to untreated controls, demonstrating a shift toward an anti-inflammatory phenotype. Collectively, we have shown for the first time in humans that ATB-346 is potently anti-inflammatory and propose that ATB-346 represents the next generation of H₂S-NSAIDs, as a viable alternative to conventional NSAIDs, with reduced adverse effects profile.

中文翻译：

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释放 H2S 的萘普生 (ATB-346) 在人体炎症模型中的有效抗炎作用

ATB-346 是一种源自萘普生的释放硫化氢的非甾体抗炎药 (H ₂ S-NSAID)，在临床前研究中已证明其具有显着减少胃肠道不良反应。然而，与萘普生相比，其在人体中的抗炎特性尚未得到证实。为了测试这一点，我们在健康的人类志愿者中使用了由紫外线杀死的大肠杆菌引发的急性炎症皮肤模型. 这种强大的模型可以量化炎症的主要迹象以及在发炎皮肤内积累的细胞和体液因素。ATB-346 在抑制环氧合酶活性以及疼痛和压痛方面不劣于萘普生。与未处理的对照相比，ATB-346 在 4 小时时显着抑制炎症部位的中性粒细胞浸润。与健康对照相比，接受 ATB-346 治疗的受试者的疼痛和压痛也显着减轻。此外，与未处理的对照相比，在 48 小时时浸润炎症部位的经典和中间单核细胞亚群表达的 CD14 水平显着降低，表明向抗炎表型转变。总的来说，₂ S-NSAIDs，作为传统 NSAIDs 的可行替代品，减少了不良反应。